Control of nucleic acid synthesis will be studied in cultured lymphocytes obtained from normal donors, patients with immunological diseases and patients with lymphocytic malignancies. Experiments are planned to assess qualitative changes in messenger RNA and DNA species synthesized by lymphocytes under varied growth conditions. The characterization of low molecular weight nascent DNA in human lymphocytes will be continued, and the role of RNA as a primer in the replication of DNA will be examined. Our previous observations of synergism between cortisol and prostaglandin E1 in the inhibition of lymphocyte DNA synthesis will be followed up by in vitro studies of lymphocytes from patients with immune diseases and malignancy. The long range goals are: 1) to gain increased understanding of the exogenous (e.g., hormonal, antigenic) and endogenous control of DNA and RNAsynthesis in normal and abnormal lymphocytes; 2) to identify characteristics of lymphocyte DNA and messenger RNA which distinguish normal from aberrent function; and 3) to exploit these differences clinically in the diagnosis and treatment of immune diseases and lymphoid malignancies.